The relationship between ultrasound microcalcifications and psammoma bodies in thyroid tumours: a single-institution retrospective study.

AIM: To investigate the diagnostic accuracy of ultrasound microcalcifications for the detection of malignancy in thyroid nodules and determine the validity of the concept that ultrasound microcalcification reflects the presence of psammoma body calcification in thyroid nodules. MATERIALS AND METHODS: The laboratory information system at University Hospital Galway, a tertiary referral hospital, was used to compile a list of patients who underwent thyroid lobectomy or complete thyroidectomy over a continuous 12-month period with both preoperative ultrasound and postoperative histology available (n=106) from January to December 2019. The haematoxylin and eosin-stained histology slides of each case were sourced and reviewed under light microscopy by a histopathologist to determine the presence of psammoma body calcification within both benign and malignant thyroid nodules. Two radiologists reviewed preoperative thyroid ultrasound images of each case independently and blindly, and reported on the presence of ultrasonographic microcalcification. RESULTS: There was a strong and significant relationship between the presence of preoperative ultrasound microcalcification and thyroid malignancy (p<0.001). Ultrasound microcalcification had a high specificity (93%) and positive predictive value (75%) for thyroid malignancy, with a diagnostic accuracy of 76%. Negative predictive value was high at 76.7%, while sensitivity was low at 42.8%. There was a strong and significant association between the presence of preoperative ultrasound microcalcification in thyroid nodules and the presence of pathological psammoma bodies on histology (p<0.001). DISCUSSION: Ultrasound microcalcification has a strong and significant association with malignancy in thyroid nodules. This study supported the theory that ultrasound microcalcification occurs secondary to the presence of psammoma bodies within thyroid nodules.

The preferences of young adults with Type 1 diabetes at clinics using a discrete choice experiment approach: the D1 Now Study.

AIM: Attending routine outpatient clinic appointments is a central self-management behaviour of individuals living with Type 1 diabetes. A large number of young adults with Type 1 diabetes disengage from diabetes services, which may contribute to poor psychosocial and diabetes outcomes. The aim of this study is to elicit preferences from young adults with Type 1 diabetes regarding clinic-related services to inform service delivery. METHODS: A discrete choice experiment was developed to understand the preferences of young adults with Type 1 diabetes for clinic-related services. RESULTS: Young adults recruited from young adult Type 1 diabetes clinics in 2016 completed the experiment (n = 105). Young adults with Type 1 diabetes showed a preference for shorter waiting times, seeing a nurse and a consultant, relative to a nurse alone, and a flexible booking system compared with fixed appointment times. Results suggest no preference for a nurse and a doctor, relative to a nurse alone, or other optional services (e.g. seeing dietitians or psychologists), type of HbA1c test and digital blood glucose diaries over paper-based diaries. CONCLUSION: This study highlights aspects of routine clinic appointments that are valued by young adults living with Type 1 diabetes, namely shorter waiting times at clinic, the option to see both a nurse and consultant at each visit and a flexible clinic appointment booking system. These findings suggest young adults with Type 1 diabetes value convenience and should help services to restructure their clinics to be more responsive to the needs of young adults.

Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) predisposes to recurrent fractures. Patients with the moderate to severe forms of OI present with antenatal fractures, and the mode of delivery that would be safest for the fetus is not known. METHODS: We conducted systematic analyses of the largest cohort of individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared among individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates, including method of delivery, on fracture-related outcomes. RESULTS: When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean delivery (CD). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CD. CONCLUSION: Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI, shows that CD is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CD should be performed only for other maternal or fetal indications, not for the sole purpose of fracture prevention in OI.Genet Med 18 6, 570-576.

Pharmacokinetics of danofloxacin and N-desmethyldanofloxacin in adult horses and their concentration in synovial fluid.

The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half-life of 8.00 ± 0.48 h. Maximum plasma concentration (Cmax ) of N-desmethyldanofloxacin (0.151 ± 0.038 µg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 µg/mL) than after IG administration (0.99 ± 0.1 µg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 µg/mL) and i.m. (0.70 ± 0.35 µg/mL) than after IG (0.20 ± 0.12 µg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 µg/mL for i.v. and i.m. administration and 0.12 µg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.

The pharmacokinetics of oclacitinib maleate, a Janus kinase inhibitor, in the dog.

The pharmacokinetics of oclacitinib maleate was evaluated in four separate studies. The absolute bioavailability study used a crossover design with 10 dogs. The effect of food on bioavailability was investigated in a crossover study with 18 dogs. The breed effect on pharmacokinetics was assessed in a crossover study in beagles and mongrels dogs. Dose proportionality and multiple dose pharmacokinetics were evaluated in a parallel design study with eight dogs per group. In all four studies, serial blood samples for plasma were collected. Oclacitinib maleate was rapidly and well absorbed following oral administration, with a time to peak plasma concentration of <1 h and an absolute bioavailability of 89%. The prandial state of dogs did not significantly affect the rate or extent of absorption of oclacitinib maleate when dosed orally, as demonstrated by the lack of significant differences in pharmacokinetic parameters between the oral fasted and oral fed treatment groups. The pharmacokinetics of oclacitinib in laboratory populations of beagles and mixed breed dogs also appeared similar. Following oral administration, the exposure of oclacitinib maleate increased dose proportionally from 0.6 to 3.0 mg/kg. Additionally, across the pharmacokinetic studies, there were no apparent differences in oclacitinib pharmacokinetics attributable to sex.

Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-α.

AIMS/HYPOTHESIS: MicroRNAs (miRNAs) are short endogenous RNAs that regulate multiple biological processes including adipogenesis and fat metabolism. We sought to identify miRNAs that correlate with BMI and to elucidate their upstream regulation and downstream targets. METHODS: Microarray-based expression profiling of 233 miRNAs was performed on subcutaneous abdominal adipose tissue biopsies from 29 non-diabetic Pima Indian participants. Correlation of the expression levels of eight miRNAs with BMI was assessed by quantitative reverse transcription (QRT) PCR in adipose samples from 80 non-diabetic Pima Indians with a BMI of 21.6-54.0 kg/m(2). The upstream regulation of one of these miRNAs, miR-221, was tested by treating cultured human pre-adipocytes with leptin, TNF-α and insulin. Predicted targets of miR-221 were validated using QRT-PCR, immunoblots and luciferase assays. The downstream effects of miR-221 overexpression were assayed by proteomic analysis. RESULTS: Expression levels of miR-221 were positively correlated with BMI (particularly in women) and fasting insulin concentrations, while the levels of miR-193a-3p and miR-193b-5p were negatively correlated with BMI; other miRNAs did not show significant associations in the 80 samples. miR-221 was downregulated by leptin and TNF-α treatment in cultured human pre-adipocytes. Conversely, miR-221 overexpression upregulated several proteins involved in fat metabolism, mimicking peroxisome proliferator-activated receptor (PPAR) activation. Furthermore, miR-221 directly downregulated the adiponectin receptor 1 (ADIPOR1) and the transcription factor v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1). Adiponectin signalling is known to promote insulin sensitivity, and ETS1 is crucial for angiogenesis. CONCLUSIONS/INTERPRETATION: Our data suggest that miR-221 may contribute to the development of the insulin resistance that typically accompanies obesity, by affecting PPAR signalling pathways and by directly downregulating ADIPOR1 and ETS1.

The structure of plastocyanin tunes the midpoint potential by restricting axial ligation of the reduced copper ion.

Blue copper proteins are models for illustrating how proteins tune metal properties. Nevertheless, the mechanisms by which the protein controls the metal site remain to be fully elucidated. A hindrance is that the closed shell Cu(I) site is inaccessible to most spectroscopic analyses. Carbon deuterium (C-D) bonds used as vibrational probes afford nonperturbative, selective characterization of the key cysteine and methionine copper ligands in both redox states. The structural integrity of Nostoc plastocyanin was perturbed by disrupting potential hydrogen bonds between loops of the cupredoxin fold via mutagenesis (S9A, N33A, N34A), variably raising the midpoint potential. The C-D vibrations show little change to suggest substantial alteration to the Cu(II) coordination in the oxidized state or in the Cu(I) interaction with the cysteine ligand. They rather indicate, along with visible and NMR spectroscopy, that the methionine ligand distinctly interacts more strongly with the Cu(I) ion, in line with the increases in midpoint potential. Here we show that the protein structure determines the redox properties by restricting the interaction between the methionine ligand and Cu(I) in the reduced state.

Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease.

Mononuclear phagocytes (monocytes, macrophages, and dendritic cells) play major roles in human immunodeficiency virus (HIV) persistence and disease pathogenesis. Macrophage antigen presentation and effector cell functions are impaired by HIV-1 infection. Abnormalities of macrophage effector cell function in bone marrow, lung, and brain likely result as a direct consequence of cellular activation and HIV replication. To further elucidate the extent of macrophage dysfunction in HIV-1 disease, a critical activation-specific regulatory molecule, nitric oxide (NO.), which may contribute to diverse pathology, was studied. Little, if any, NO. is produced by uninfected human monocytes. In contrast, infection with HIV-1 increases NO. production to modest, but significant levels (2-5 microM). Monocyte activation (with lipopolysaccharide, tumor necrosis factor alpha, or through interactions with astroglial cells) further enhances NO. production in HIV-infected cells, whereas its levels are diminished by interleukin 4. These results suggest a possible role for NO. in HIV-associated pathology where virus-infected macrophages are found. In support of this hypothesis, RNA encoding the inducible NO synthase (iNOS) was detected in postmortem brain tissue from one pediatric AIDS patient with advanced HIV encephalitis. Corresponding iNOS mRNA was not detected in brain tissue from five AIDS patients who died with less significant brain disease. These results demonstrate that HIV-1 can influence the expression of NOS in both cultured human monocytes and brain tissue. This newly described feature of HIV-macrophage interactions suggests previously unappreciated mechanisms of tissue pathology that result from productive viral replication.

Perspectives of board certified pediatric dentists on adding a pediatric oral health therapist to the dental team.

PURPOSE: The purpose of this study was to determine the perspectives of board certified pediatric dentists regarding adding a pediatric oral health therapist/dental therapist to the dental team. METHODS: A 27-item online survey was e-mailed to all diplomates of the American Board of Pediatric Dentistry Questions assessed knowledge and opinions regarding the concept of a pediatric oral health therapist, as well as perspectives on the parameters under which such a person could practice. Survey results were tabulated and frequency distributions calculated. RESULTS: Seventy-five percent of respondents had limited or no knowledge regarding the concept of a pediatric oral health therapist; 79% had limited or no knowledge regarding the use of dental therapists in Alaska. Seventy-one percent disagreed with adding a therapist to the dental team. Pediatric dentists practicing in the public sector were more knowledgeable and supportive. Sixty-six percent indicated they treated children with Medicaid/CHIP insurance. Of those, most disagreed that therapists would enable them to care far more children. CONCLUSIONS: Pediatric dentists are generally not knowledgeable regarding the role of therapists internationally Nevertheless, the majority oppose adding such an individual to the dental team in the United States.

Genetic analysis of digestive physiology using fluorescent phospholipid reporters.

Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. Genetic screening identifies zebrafish mutants, such as fat free, that show normal digestive organ morphology but severely reduced phospholipid and cholesterol processing. Thus, fluorescent lipids provide a sensitive readout of lipid metabolism and are a powerful tool for identifying genes that mediate vertebrate digestive physiology.

Assessment of Explicitly Stated Interval Change on Noncontrast Head CT Radiology Reports.

BACKGROUND AND PURPOSE: Consistent and standardized reporting of interval change for certain diagnoses may improve the clinical utility of radiology reports. The purpose of this study was to assess explicitly stated interval change of various findings in noncontrast head CT reports. MATERIALS AND METHODS: A retrospective review was performed on successive noncontrast head CT radiology reports from the first 2 weeks of January 2014. Reports with at least 1 prior comparison CT scan were included. Reports with normal examination findings and those that made comparison with only other types of examinations (eg, MR imaging) were excluded. Descriptive and subgroup statistical analyses were performed. RESULTS: In total, 200 patients with 230 reports and 979 radiographic findings were identified. The average interval between reports was 344.9 ± 695.9 days (range, 0-3556 days). Interval change was mentioned 67.3% (n = 659) of the time for all findings (n = 979). Explicitly stated interval change was significantly associated with nonremote findings (P < .001) and generalized statements of interval change (P < .001). The proportion of interval change reported ranged from 95.3% of the time for hemorrhagic to 36.4% for soft-tissue/osseous categorizations. CONCLUSIONS: Interval change reporting was variable, mentioned for 67.3% of noncontrast head CT report findings with a prior comparison CT scan. Structured radiology reports may improve the consistent and clear reporting of interval change for certain findings.

Development of noradrenergic neurons in the zebrafish hindbrain requires BMP, FGF8, and the homeodomain protein soulless/Phox2a.

We report that the zebrafish mutation soulless, in which the development of locus coeruleus (LC) noradrenergic (NA) neurons failed to occur, disrupts the homeodomain protein Phox2a. Phox2a is not only necessary but also sufficient to induce Phox2b+ dopamine-beta-hydroxylase+ and tyrosine hydroxylase+ NA neurons in ectopic locations. Phox2a is first detected in LC progenitors in the dorsal anterior hindbrain, and its expression there is dependent on FGF8 from the mid/hindbrain boundary and on optimal concentrations of BMP signal from the epidermal ectoderm/future dorsal neural plate junction. These findings suggest that Phox2a coordinates the specification of LC in part through the induction of Phox2b and in response to cooperating signals that operate along the mediolateral and anteroposterior axes of the neural plate.

Mutational approaches to studying embryonic pattern formation in the zebrafish.

The induction and isolation of mutations in genes playing important roles in pattern formation have been extremely valuable in elucidating the mechanisms governing pattern formation in invertebrates. The recent establishment of genetic methods in the zebrafish, Brachydanio rerio, has permitted systematic mutational studies of vertebrate embryonic development.

Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate.

BACKGROUND: In Drosophila melanogaster and Caenorhabditis elegans, the elucidation of developmental mechanisms has relied primarily on the systematic induction and isolation of mutations in genes with specific functions in development. Such an approach has not yet been possible in a vertebrate species, owing to the difficulty of analyzing and keeping a sufficiently high number of mutagenized lines of animals. RESULTS: We have developed the methods necessary to perform large-scale saturation screens for mutations affecting embryogenesis in the zebrafish, Danio (Brachydanio) rerio. Firstly, a new aquarium system was developed to raise and keep large numbers of strains of genetically different fish safely and with little maintenance care. Secondly, by placing adult male fish in water containing the chemical mutagen, ethylnitrosourea, we induced point mutations in premeiotic germ cells with a rate of one to three mutations per locus per 1,000 mutagenized haploid genomes. This rate, which is similar to the mutagenesis rates produced by ethylmethanesulfonate in Drosophila, was determined for alleles at four different pigmentation genes. Finally, in a pilot screen in which mutagenized fish were inbred for two generations and scored for embryonic mutants, we isolated 100 recessive mutations with phenotypes visible in the homozygous embryos. CONCLUSION: The high rate of induction and recovery of point mutations, in addition to an efficient aquarium system to house large numbers of mutagenized lines, means that it is now possible to perform saturation mutagenesis screens in a vertebrate, similar to those done in invertebrates.

Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen.

Elevated levels of homocysteine are associated with an increased risk of atherosclerosis and thrombosis. The reactivity of the sulfhydryl group of homocysteine has been implicated in molecular mechanisms underlying this increased risk. There is also increasingly compelling evidence that thiols react in the presence of nitric oxide (NO) and endothelium-derived relaxing factor (EDRF) to form S-nitrosothiols, compounds with potent vasodilatory and antiplatelet effects. We, therefore, hypothesized that S-nitrosation of homocysteine would confer these beneficial bioactivities to the thiol, and at the same time attenuate its pathogenicity. We found that prolonged (> 3 h) exposure of endothelial cells to homocysteine results in impaired EDRF responses. By contrast, brief (15 min) exposure of endothelial cells, stimulated to secrete EDRF, to homocysteine results in the formation of S-NO-homocysteine, a potent antiplatelet agent and vasodilator. In contrast to homocysteine, S-NO-homocysteine does not support H2O2 generation and does not undergo conversion to homocysteine thiolactone, reaction products believed to contribute to endothelial toxicity. These results suggest that the normal endothelium modulates the potential, adverse effects of homocysteine by releasing EDRF and forming the adduct S-NO-homocysteine. The adverse vascular properties of homocysteine may result from an inability to sustain S-NO formation owing to a progressive imbalance between the production of NO by progressively dysfunctional endothelial cells and the levels of homocysteine.

Microtubule-associated targets in chlorpyrifos oxon hippocampal neurotoxicity.

Prolonged exposure to organophosphate (OP) pesticides may produce cognitive deficits reflective of hippocampal injury in both humans and rodents. Recent work has indicated that microtubule trafficking is also adversely affected by exposure to the OP pesticide chlorpyrifos, suggesting a novel mode of OP-induced neurotoxicity. The present studies examined effects of prolonged exposure to chlorpyrifos oxon (CPO) on acetylcholinesterase (AChE) activity, immunoreactivity (IR) of microtubule-associated proteins, neuronal injury, and tubulin polymerization using in vitro organotypic slice cultures of rat hippocampus and bovine tubulin. Cultures were exposed to CPO (0.1-10 microM) in cell culture medium for 1-7 days, a regimen producing progressive reductions in AChE activity of 15-60%. Cytotoxicity (somatic uptake of the non-vital marker propidium iodide), as well as IR of alpha-tubulin and microtubule-associated protein-2 (a/b) [MAP-2], was assessed 1, 3, and 7 days after the start of CPO exposure. As early as 24 h after the start of exposure, CPO-induced deficits in MAP-2 IR were evident and progressive in each region of slice cultures at concentrations as low as 0.1 microM. CPO exposure did not alter alpha-tubulin IR at any time point. Concentration-dependent injury in the cornu ammonis (CA)1 pyramidal cell layer and to a lesser extent, CA3 and dentate cells, was evident 3 days after the start of CPO exposure (>or=0.1 microM) and was greatest after 7 days. Tubulin polymerization assays indicated that CPO (>or=0.1 microM) markedly inhibited the polymerization of purified tubulin and MAP-rich tubulin, though effects on MAP-rich tubulin were more pronounced. These data suggest that exposure to CPO produces a progressive decrease in neuronal viability that may be associated with impaired microtubule synthesis and/or function.

Improved detection of skull metastasis with diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Metastasis to the skull is clinically important, but routine MR imaging offers moderate sensitivity for skull-metastasis detection in our experience. We sought to determine if diffusion-weighted MR imaging (DWI) could improve the detection of skull metastasis in patients with primary carcinomas that metastasized to bone compared with conventional MR imaging. MATERIALS AND METHODS: Seventy-five patients from the tumor registry of our institution with extracranial primary malignancy who had brain MR imaging with DWI and radionuclide bone scanning (RNBS, gold standard) within a 6-week interval were evaluated. Thirty-eight patients demonstrated increased radiopharmaceutical uptake on RNBS, consistent with skull metastasis of any size, and the remaining 37 were control subjects. Two readers correlated the DWI and conventional MR imaging with RNBS. RESULTS: The overall sensitivity of DWI for detection of skull metastases was 68.4%-71.1% (kappa=0.68) versus 42.1%-55.3% (kappa=0.65) for conventional MR imaging. Breast cancer (n=20) was detected with greatest sensitivity of 86.7%-93.3% (kappa=0.80) for DWI versus 60%-80% (kappa=0.5) for conventional MR imaging. Lung cancer (n=32) was detected with 63.6%-72.7% sensitivity (kappa=0.56), and prostate cancer (n=8) with 14.3% sensitivity (kappa=0.5) for DWI versus 27.3%-36.4% (kappa=0.81) and 14.3-42.9% (kappa=0), respectively, for conventional MR imaging. CONCLUSIONS: DWI is a useful sequence for identifying focal skull metastases for breast and lung malignancies and, compared with conventional MR imaging, provides improved detection of these lesions. DWI is insensitive for detecting skull metastases from prostate carcinoma.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the D1 Now Study.

PLAIN ENGLISH SUMMARY: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants. A 3-day international conference was held in Galway in June 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". It aimed to bring together people from a broad variety of backgrounds with an interest in young adults with type 1 diabetes. Young people with type 1 diabetes came together with healthcare professionals, researchers, software developers and policy makers to come up with and agree on a new approach for engaging young adults with type 1 diabetes with their health services and to improve how they manage their diabetes.The people involved in the conference aimed to reach agreement (consensus) on a fixed set of outcome measures called a core outcome set (COS) that the group would recommend future studies involving young adults with type 1 diabetes to use, to suggest a new approach (intervention) for providing health services to young adults with type 1 diabetes, and to come up with health technology ideas that could help deliver the new intervention. Over the 3 days, this diverse international group of people that included young adults living with type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1 possible health technology idea that could help with how the overall intervention could be delivered.Involving young adults living with type 1 diabetes in a 3-day conference along with other key groups is an effective method for coming up with a new approach to improve health services for young adults with type 1 diabetes and better support their self-management. ABSTRACT: Background A 3-day international consensus meeting was hosted by the D1 Now study team in Galway on June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". The aim of the meeting was to bring together young adults with type 1 diabetes, healthcare providers, policy makers and researchers to reach a consensus on strategies to improve engagement, self-management and ultimately outcomes for young adults living with type 1 diabetes. Methods This diverse stakeholder group participated in the meeting to reach consensus on (i) a core outcome set (COS) to be used in future intervention studies involving young adults with type 1 diabetes, (ii) new strategies for delivering health services to young adults and (iii) potential digital health solutions that could be incorporated into a future intervention. Results A COS of 8 outcomes and 3 key intervention components that aim to improve engagement between young adults with type 1 diabetes and service providers were identified. A digital health solution that could potentially compliment the intervention components was proposed. Conclusion The outputs from the 3-day consensus conference, that held patient and public involvement at its core, will help the research team further develop and test the D1 Now intervention for young adults with type 1 diabetes in a pilot and feasibility study and ultimately in a definitive trial. The conference represents a good example of knowledge exchange among different stakeholders for health research and service improvement.

Improved detection of metastatic melanoma by T2*-weighted imaging.

BACKGROUND AND PURPOSE: The imaging features of metastatic melanomas are distinctive due to the presence of melanin and the propensity for hemorrhage. Both hemorrhage and melanin can produce T1-weighted hyperintensity and T2*-weighted signal intensity loss. We hypothesized that T2*-weighted images would improve detection of metastatic melanoma. METHODS: The T2* and T1 characteristics of 120 newly detected metastatic brain lesions from 31 patients with malignant melanoma were compared with those of 120 brain metastases from 23 patients with lung cancer. RESULTS: Melanoma metastases were 5 times more likely to demonstrate prominent T2*-related signal intensity loss (susceptibility effect) than were lung metastases (42% vs 8%; P < .01), and 4.5 times more likely to demonstrate T1 hyperintensity (55% vs 12%; P < .01). Patients with melanoma had lesions that were either hypointense on T2*-weighted images, hyperintense on T1 images, or both, in 71% (85/120), compared with 19% (23/120) of lung carcinoma metastases (P < .01). Melanoma lesions were 16 times more likely than lung cancer lesions to show combined T2* related signal intensity loss and T1 hyperintensity (P < .01). Remarkably, 8 melanoma lesions (7%) in 3 patients were detectable principally on the T2*-weighted sequences, whereas no lung cancer lesion was detected solely on susceptibility images. We found a direct correlation between melanin content and T1 hyperintensity but no correlation between T2* intensity and melanin. CONCLUSION: T2*-weighted images improve lesion detection in patients with melanoma metastases, and in conjunction with T1-weighted sequences, can suggest melanoma as the etiology of an intracranial mass. This sequence should be employed for evaluation of possible brain metastasis in patients without a known primary malignancy and in studies for melanoma staging.